1. Field of the Invention
The invention generally relates to articles having bioactive surfaces, as well as solvent-free methods of preparation. The invention more particularly relates to preparing articles having bioactive surfaces by solvent-free deposition of a monomer onto the surface of a substrate having free reactive groups, and then covalently immobilizing a biologically functional molecule onto the monomer-deposited substrate.
2. Background of the Invention
Any surface of a non-biological origin initiates a sequence of unwanted reactions when brought into contact with living tissue or blood. The most well known reactions are those generated by the blood-contacting materials that activate the platelets and the plasma coagulation system leading the formation of a thrombus. Foreign surfaces in living tissue activate the complement and the mononuclear cell systems, thereby creating inflammatory reactions. To overcome these unwanted reactions, surfaces must be rendered biocompatible, prior to the use in vivo.
The importance of biocompatible surfaces, i.e. surfaces that are stable in a biological environment, is well known and has been sought after for many years and through a variety of approaches. Biocompatible surfaces are needed for medical devices that are to be implanted for extended time periods. It is well-known that, generally speaking, biocompatibility properties are enhanced by attempting to secure biologically active agents to surfaces of medical devices, particularly those which contact tissue, including blood, when they are implanted or otherwise used during medical procedures and the like. Furthermore, it may be undesirable to have the biologically active agent leach away in wet environments, such as are encountered in blood or other body fluids.
Additionally, it is equally desirable to use biocompatible surfaces in in vitro settings. Biocompatible surfaces can be used to mimic or approximate in vivo settings, for example, to promote in vitro cell survival, proliferation or differentiation. Additionally, the biocompatible surfaces can be used in an in vitro setting to screen the effects of molecules, such as drugs, drug candidates, proteins, mutant proteins, etc. on cells or tissues, prior to the administration to a subject.
Many approaches to preparing biocompatible surfaces concentrate on utilizing polymeric surfaces as the surface which encounters the body fluids or cell culture fluids, and then treating those polymeric surfaces according to a variety of procedures. Other approaches treat metallic surfaces that are intended to contact body fluids during implantation and the like.
Generally speaking, the types of treatments that have been implemented or attempted fall into three broad categories. One involves plasma discharge treatments of the medical device surface. Another involves immersing or similar means for contacting the surface with specific chemical components under treatment conditions (such as elevated temperature), which are less elaborate than plasma discharge treatments. The third general type of treatment typically involves chemically oxidizing the surface (usually metal), until enough of an oxide layer is provided for bonding.
Current methods for producing biocompatible surfaces utilize solution phase chemistry, where a component (monomer) that is coated onto the surface is dissolved in solvent. Solvents, however, can often times harm the surface being treated, or they can harm or denature the biologically active molecule being immobilized. For example, when plastics are being rendered biocompatible, the use of organic solvents may destroy the plastic surface.
Thus there is a need in the art for a process of treating surfaces without the use of solvent. These treated surfaces can further be rendered biocompatible for use in an in vivo or an in vitro setting.